Background: Current treatments of lipopolysaccharide (LPS)-induced acute lung injury (ALI) are unsatisfactory due to the insufficient understanding of the pathogenesis of LPS-induced ALI. The NLRP3 inflammasome is an essential part of the innate protection system and is involved in LPS-induced ALI; however, comprehensive understanding of molecular pathogenesis of the disease is lacking. Our study explored the effect of heme oxygenase-1 (HO-1) on NLRP3 inflammasomes in vitro.
Methods: Alveolar macrophages (NR8383) were preincubated with high-mobility group box-1 (HMGB1) or HO-1 CRISPR plasmids before LPS stimulation. Then, we detected the effect of HO-1 on NLRP3 inflammasomes.
Results: Our study demonstrates that the activation of HO-1 represses the level of NLRP3 inflammasomes and the subsequent increases of the level of IL-1β. Moreover, NLRP3 inflammasome activation was sensitive to the HMGB1 activity, and HO-1 was able to reduce the amount of HMGB1 released. Furthermore, downregulation of NLRP3 inflammasomes was related to NADPH quinone oxidoreductase 1 (an HO-1-related gene).
Conclusions: Our study clarifies the constrained coordination of the HO-1 signal in the HMGB1-mediated activation of NLRP3 inflammasomes in NR8383 alveolar macrophages after LPS stimulation.
Keywords: HMGB1; HO-1; Lipopolysaccharide; NLRP3 inflammasome; NR8383 AMs.
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